A Pick-Me-Up for Cancer

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Science  22 Sep 2006:
Vol. 313, Issue 5794, pp. 1704
DOI: 10.1126/science.313.5794.1704b

A major avenue that is being explored in the treatment of cancer is the possibility of mobilizing the immune system to attack tumor cells. However, for reasons that are only slowly becoming clear, encouraging immune cells to destroy tumors remains relatively inefficient.

Ohta et al. provide evidence that tumors protect themselves from immune attack via extracellular adenosine generated within the hypoxic environment of the tumor mass itself. Previous studies have suggested that during inflammation, the activation of the adenosine receptor (A2AR) on T cells leads to levels of intracellular cyclic AMP that inhibit cell function. In the current experiments, 60% of mice lacking A2AR rejected their tumors, as compared to unimpaired tumor growth seen in mice with immune cells able to signal through the receptor. A2AR antagonists—including caffeine—had similar, albeit less robust, tumor-inhibiting effects that depended on interferon-γ-producing CD8+ T cells. These results lend support to the contested notion that the immune system continuously monitors for malignancy and raises the question of an A2AR-mediated contribution to early spontaneous tumor growth. If this is the case, then inhibition of this pathway might be helpful as an adjunct to immune-based therapies for some cancers. — SJS

Proc. Natl. Acad. Sci. U.S.A. 103, 13132 (2006).

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